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AimsThe intermediate-term effects of dietary protein on cardiometabolic risk factors in overweight and obese patients with heart failure and diabetes mellitus are unknown. We compared the effect of two calorie-restricted diets on cardiometabolic risk factors in this population.Methods and resultsIn this randomized controlled study, 76 overweight and obese (mean weight, 107.8 ± 20.8 kg) patients aged 57.7 ± 9.7 years, 72.4% male, were randomized to a high-protein (30% protein, 40% carbohydrates, and 30% fat) or standard-protein diet (15% protein, 55% carbohydrates, and 30% fat) for 3 months. Reductions in weight and cardiometabolic risks were evaluated at 3 months. Both diets were equally effective in reducing weight (3.6 vs. 2.9 kg) and waist circumference (1.9 vs. 1.3 cm), but the high-protein diet decreased to a greater extent glycosylated haemoglobin levels (0.7% vs. 0.1%, P = 0.002), cholesterol (16.8 vs. 0.9 mg/dL, P = 0.031), and triglyceride (25.7 vs. 5.7 mg/dL, P = 0.032), when compared with the standard-protein diet. The high-protein diet also significantly improved both systolic and diastolic blood pressure than the standard-protein diet (P

The prebiotic potential of nervine herbal medicines has been scarcely studied. We therefore used anaerobic human fecal cultivation to investigate whether medicinal herbs commonly used as treatment in neurological health and disease in Ayurveda and other traditional systems of medicine modulate gut microbiota. Profiling of fecal cultures supplemented with either Kapikacchu, Gotu Kola, Bacopa/Brahmi, Shankhapushpi, Boswellia/Frankincense, Jatamansi, Bhringaraj, Guduchi, Ashwagandha or Shatavari by 16S rRNA sequencing revealed profound changes in diverse taxa. Principal coordinate analysis highlights that each herb drives the formation of unique microbial communities predicted to display unique metabolic potential. The relative abundance of approximately one-third of the 243 enumerated species was altered by all herbs. Additional species were impacted in an herb-specific manner. In this study, we combine genome reconstruction of sugar utilization and short chain fatty acid (SCFA) pathways encoded in the genomes of 216 profiled taxa with monosaccharide composition analysis of each medicinal herb by quantitative mass spectrometry to enhance the interpretation of resulting microbial communities and discern potential drivers of microbiota restructuring. Collectively, our results indicate that gut microbiota engage in both protein and glycan catabolism, providing amino acid and sugar substrates that are consumed by fermentative species. We identified taxa that are efficient amino acid fermenters and those capable of both amino acid and sugar fermentation. Herb-induced microbial communities are predicted to alter the relative abundance of taxa encoding SCFA (butyrate and propionate) pathways. Co-occurrence network analyses identified a large number of taxa pairs in medicinal herb cultures. Some of these pairs displayed related culture growth relationships in replicate cultures highlighting potential functional interactions among medicinal herb-induced taxa.

Limited studies have investigated the role of the microbiota in hypertensive disorders of pregnancy (HDP), particularly preeclampsia, which often results in preterm birth. We evaluated 23 studies that explored the relationship between gut, vaginal, oral, or placental microbiotas and HDP. Scopus, ProQuest Health Research Premium Collection, ProQuest Nursing & Allied Health Database, EBSCO, and Ovid were searched for relevant literature. Majority (18) of studies focused on the gut microbiota, and far fewer examined the oral cavity (3), vagina (3), and placenta (1). One study examined the gut, oral, and vaginal microbiotas. The consensus highlights a potential role for microbiota dysbiosis in preeclampsia and HDP. Especially in the third trimester, preeclampsia is associated with gut dysbiosis—deficient in beneficial species of Akkermansia, Bifidobacterium, and Coprococcus but enriched with pathogenic Campylobacterota and Candidatus Saccharibacteria, with low community α‐diversity. Similarly, the preeclamptic vaginal and oral microbiotas are enriched with bacterial vaginosis and periodontal disease‐associated species, respectively. The trend is also observed in the placenta, which is colonized by gastrointestinal, respiratory tract, and periodontitis‐related pathogens. Consequently, a chronic proinflammatory state that adversely impacts placentation is implicated. These observations however require more mechanistic studies to establish the timing of the preceding immune dysfunction and any causality. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) continues to cause morbidity and mortality worldwide; therefore, effective treatments remain crucial to controlling it. As interferon-alpha (IFN-α) and -beta (β) have been proposed as COVID-19 treatments, we sought to assess their effectiveness on respiratory, cardiovascular, neurological, and psychiatric signs and symptoms, as well as PASC and death, in hospitalized COVID-19 patients without multiple sclerosis (MS). Using a federated data research network (TriNetX), we performed a retrospective cohort study of hospitalized COVID-19 patients without MS who received IFN-α or -β treatment, comparing them to a similar cohort who did not receive treatment. Following propensity-score matched analyses, we demonstrate that hospitalized COVID-19 patients who were treated with IFN-α or -β had significantly higher odds of death. In contrast, there was no significant difference in any other outcomes between 1–30 days or 1 day to anytime afterward. Overall, hospitalized COVID-19 patients without MS who were treated with IFN-α or -β had similar short- and long-term sequelae (except for mortality) as those who did not receive treatment. The potential benefits of utilizing IFN-α or -β treatment as therapeutics remain to be realized, and our research highlights the need to explore repurposing drugs for COVID-19 using real-world evidence. [ABSTRACT FROM AUTHOR]

Abstract Background Identification of complex multidimensional interaction patterns within microbial communities is the key to understand, modulate, and design beneficial microbiomes. Every community has members that fulfill an essential function affecting multiple other community members through secondary metabolism. Since microbial community members are often simultaneously involved in multiple relations, not all interaction patterns for such microorganisms are expected to exhibit a visually uninterrupted pattern. As a result, such relations cannot be detected using traditional correlation, mutual information, principal coordinate analysis, or covariation-based network inference approaches. Results We present a novel pattern-specific method to quantify the strength and estimate the statistical significance of two-dimensional co-presence, co-exclusion, and one-way relation patterns between abundance profiles of two organisms as well as extend this approach to allow search and visualize three-, four-, and higher dimensional patterns. The proposed approach has been tested using 2380 microbiome samples from the Human Microbiome Project resulting in body site-specific networks of statistically significant 2D patterns as well as revealed the presence of 3D patterns in the Human Microbiome Project data. Conclusions The presented study suggested that search for Boolean patterns in the microbial abundance data needs to be pattern specific. The reported presence of multidimensional patterns (which cannot be reduced to a combination of two-dimensional patterns) suggests that multidimensional (multi-organism) relations may play important roles in the organization of microbial communities, and their detection (and appropriate visualization) may lead to a deeper understanding of the organization and dynamics of microbial communities. Video Abstract

We previously reported that microRNA (miR)23a and miR30b are selectively sorted into exosomes derived from rickettsia‐infected endothelial cells (R‐ECExos). Yet, the mechanism remains unknown. Cases of spotted fever rickettsioses have been increasing, and infections with these bacteria cause life‐threatening diseases by targeting brain and lung tissues. Therefore, the goal of the present study is to further dissect the molecular mechanism underlying R‐ECExos‐induced barrier dysfunction of normal recipient microvascular endothelial cells (MECs), depending on their exosomal RNA cargos. Infected ticks transmit the rickettsiae to human hosts following a bite and injections of the bacteria into the skin. In the present study, we demonstrate that treatment with R‐ECExos, which were derived from spotted fever group R parkeri infected human dermal MECs, induced disruptions of the paracellular adherens junctional protein VE‐cadherin, and breached the paracellular barrier function in recipient pulmonary MECs (PMECs) in an exosomal RNA‐dependent manner. We did not detect different levels of miRs in parent dermal MECs following rickettsial infections. However, we demonstrated that the microvasculopathy‐relevant miR23a‐27a‐24 cluster and miR30b are selectively enriched in R‐ECExos. Bioinformatic analysis revealed that common sequence motifs are shared exclusively among the exosomal, selectively‐enriched miR23a cluster and miR30b at different levels. Taken together, these data warrant further functional identification and characterization of a monopartition, bipartition, or tripartition among ACA, UCA, and CAG motifs that guide recognition of microvasculopathy‐relevant miR23a‐27a‐24 and miR30b, and subsequently results in their selective enrichments in R‐ECExos. [ABSTRACT FROM AUTHOR]